Ras-associated protein-1 （Rapl）, a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions （e.g., formation and control of cell adhesions and junctions）, cellular migr...Ras-associated protein-1 （Rapl）, a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions （e.g., formation and control of cell adhesions and junctions）, cellular migration, and polarization. Through its interaction with other proteins, Rapl plays many roles during cell invasion and metastasis in different cancers. The basic function of Rapl is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate （GTP） or guanosine diphosphate （GDP）. However, its remarkably diverse function is rendered by its interplay with a large number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizes the mechanisms by which Rap 1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherin regulation, Rho GTPase control, and matrix metalloproteinase expression.展开更多
Rapl is expressed in human umbilical vein endothelial cells （HUVECs）. Rapl-GTPase activating protein （RaplGAP）, with its specific target, Rapl, has been shown to be important in the regulation of many physiologica...Rapl is expressed in human umbilical vein endothelial cells （HUVECs）. Rapl-GTPase activating protein （RaplGAP）, with its specific target, Rapl, has been shown to be important in the regulation of many physiological and certain pathological processes. In this study, we investigated the effect of RaplGAP expression on endothelial cell function, or, more specifically, proliferation and migration of endothelial cells. HUVECs were transfected with pcDNA3.1 （empty vector）, pcDNA3.1 containing Flag-tagged-RaplGAP or Myc-tagged-RaplN17. The proliferation, migration and tube formation were examined and compared among the 3 groups. Expression of Rapl, RaplGAP, extracellular signal-regulated kinase （ERK）, phospho-ERK, Akt, phosphor-Akt was detected by Western blotting. The results showed that the proliferation, migration and tube formation were significantly reduced in RaplGAP- and RaplN17-transfected HUVECs as compared with empty vector-transfected control. These changes were coincident with increased expression of Rap 1GAP and decreased expression of activated Rap l, phospho-ERK and -Akt. After treatment of Rap l GAP-transfected HUVECs with a stimulator of Rapl guanine-nucleotide-exchange factor （RaplGEF） 8CPT-2＇OMe-cAMP, it was found that Rapl activity was decreased as compared with empty vector-transfected control. Pretreatment of HU- VECs with an ERK inhibitor PD98059 or a PI3K inhibitor LY294002 prior to stimulation not only blocked 8CPT-2＇OMe-cAMP-induced phosphorylation of ERK and Akt, but also significantly reduced cell proliferation and migration. Finally, we examined the effect of vascular endothelial growth factor （VEGF） on HUVECs overexpressing RaplGAP. VEGF-stimulated Rapl activity, phosphorylation of ERK and Akt, cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing RaplGAP as compared to empty vector-transfected Control. Taken together, our findings demonstrate that RaplGAP/Rapl and their downstream effectors regulate proliferation and migration of HUVECs via ERK and Akt pathways.展开更多
To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to maximize energy sa...To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to maximize energy savings under a given performance degradation. Machine learning techniques were utilized to develop performance models which would provide accurate performance prediction with change in operating core-uncore frequency. Experiments, performed on a node (28 cores) of a modern computing platform showed significant energy savings of as much as 26% with performance degradation of as low as 5% under the proposed strategy compared with the execution in the unlimited power case.展开更多
To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to distribute a given...To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to distribute a given power allocation among the cluster nodes assigned to the application while balancing their performance change. The strategy operates in a timeslice-based manner to estimate the current application performance and power usage per node followed by power redistribution across the nodes. Experiments, performed on four nodes (112 cores) of a modern computing platform interconnected with Infiniband showed that even a significant power budget reduction of 20% may result in a performance degradation of as low as 1% under the proposed strategy compared with the execution in the unlimited power case.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.31271504 and 31471310)the Shenzhen Science and Technology Innovation Committee,China(Grant No.JCYJ2013040 1144744187)
文摘Ras-associated protein-1 （Rapl）, a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions （e.g., formation and control of cell adhesions and junctions）, cellular migration, and polarization. Through its interaction with other proteins, Rapl plays many roles during cell invasion and metastasis in different cancers. The basic function of Rapl is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate （GTP） or guanosine diphosphate （GDP）. However, its remarkably diverse function is rendered by its interplay with a large number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizes the mechanisms by which Rap 1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherin regulation, Rho GTPase control, and matrix metalloproteinase expression.
基金supported by grants from the National Natural Science Foundation of China(No.30971207)Natural Science Foundation of Hubei Province,China(No.2009CBD-386)
文摘Rapl is expressed in human umbilical vein endothelial cells （HUVECs）. Rapl-GTPase activating protein （RaplGAP）, with its specific target, Rapl, has been shown to be important in the regulation of many physiological and certain pathological processes. In this study, we investigated the effect of RaplGAP expression on endothelial cell function, or, more specifically, proliferation and migration of endothelial cells. HUVECs were transfected with pcDNA3.1 （empty vector）, pcDNA3.1 containing Flag-tagged-RaplGAP or Myc-tagged-RaplN17. The proliferation, migration and tube formation were examined and compared among the 3 groups. Expression of Rapl, RaplGAP, extracellular signal-regulated kinase （ERK）, phospho-ERK, Akt, phosphor-Akt was detected by Western blotting. The results showed that the proliferation, migration and tube formation were significantly reduced in RaplGAP- and RaplN17-transfected HUVECs as compared with empty vector-transfected control. These changes were coincident with increased expression of Rap 1GAP and decreased expression of activated Rap l, phospho-ERK and -Akt. After treatment of Rap l GAP-transfected HUVECs with a stimulator of Rapl guanine-nucleotide-exchange factor （RaplGEF） 8CPT-2＇OMe-cAMP, it was found that Rapl activity was decreased as compared with empty vector-transfected control. Pretreatment of HU- VECs with an ERK inhibitor PD98059 or a PI3K inhibitor LY294002 prior to stimulation not only blocked 8CPT-2＇OMe-cAMP-induced phosphorylation of ERK and Akt, but also significantly reduced cell proliferation and migration. Finally, we examined the effect of vascular endothelial growth factor （VEGF） on HUVECs overexpressing RaplGAP. VEGF-stimulated Rapl activity, phosphorylation of ERK and Akt, cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing RaplGAP as compared to empty vector-transfected Control. Taken together, our findings demonstrate that RaplGAP/Rapl and their downstream effectors regulate proliferation and migration of HUVECs via ERK and Akt pathways.
文摘To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to maximize energy savings under a given performance degradation. Machine learning techniques were utilized to develop performance models which would provide accurate performance prediction with change in operating core-uncore frequency. Experiments, performed on a node (28 cores) of a modern computing platform showed significant energy savings of as much as 26% with performance degradation of as low as 5% under the proposed strategy compared with the execution in the unlimited power case.
文摘To improve the power consumption of parallel applications at the runtime, modern processors provide frequency scaling and power limiting capabilities. In this work, a runtime strategy is proposed to distribute a given power allocation among the cluster nodes assigned to the application while balancing their performance change. The strategy operates in a timeslice-based manner to estimate the current application performance and power usage per node followed by power redistribution across the nodes. Experiments, performed on four nodes (112 cores) of a modern computing platform interconnected with Infiniband showed that even a significant power budget reduction of 20% may result in a performance degradation of as low as 1% under the proposed strategy compared with the execution in the unlimited power case.
